The purpose of this research project is to study the factors that regulate Na movement across epithelia. Measurement of the permeability of the luminal membrane to Na revealed that is the rate-limiting step for trans-epithelial transport. The permeability appears to be regulated by intracellular Na. An increase in intracellular Na inhibits Na movement across the luminal border. Preliminary evidence suggests that an increase in intracellular Na leads to an increase in calcium movement into the cell and that it is calcium that appears to regulate the permeability of the luminal border. We plan to study directly the uptake of calcium by the epithelium and its relation to sodium movement across the luminal border and intracellular Na concentration. The role of ATP, ADP and Pi in regulating the movement of Na across the basolateral surface will be studied using a newly devised method. It appears that Na transport is regulated by the ratio of ATP to ADP and Pi rather than any single factor.